Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase
Introduction Valproic acid is an effective first line drug for the treatment of epilepsy. Hepatotoxicity is a rare and potentially fatal adverse reaction for this medicine. Objective Firstly to characterise valproic acid reports on children with fatal outcome and secondly to determine reporti...
| Main Authors: | , , |
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| Format: | Article |
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Public Library of Science
2014
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| Online Access: | https://eprints.nottingham.ac.uk/37196/ |
| _version_ | 1848795411958988800 |
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| author | Star, Kristina Edwards, I. Ralph Choonara, Imti |
| author_facet | Star, Kristina Edwards, I. Ralph Choonara, Imti |
| author_sort | Star, Kristina |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Introduction
Valproic acid is an effective first line drug for the treatment of epilepsy. Hepatotoxicity is a rare and potentially fatal adverse reaction for this medicine.
Objective
Firstly to characterise valproic acid reports on children with fatal outcome and secondly to determine reporting over time of hepatotoxicity with fatal outcome.
Methods
Individual case safety reports (ICSRs) for children ≤17 years with valproic acid and fatal outcome were retrieved from the WHO Global ICSR database, VigiBase, in June 2013. Reports were classified into hepatotoxic reactions or other reactions. Shrinkage observed-to-expected ratios were used to explore the relative reporting trend over time and for patient age. The frequency of polytherapy, i.e. reports with more than one antiepileptic medicine, was investigated.
Results
There have been 268 ICSRs with valproic acid and fatal outcome in children, reported from 25 countries since 1977. A total of 156 fatalities were reported with hepatotoxicity, which has been continuously and disproportionally reported over time. There were 31 fatalities with pancreatitis. Other frequently reported events were coma/encephalopathy, seizures, respiratory disorders and coagulopathy. Hepatotoxicity was disproportionally and most commonly reported in children aged 6 years and under (104/156 reports) but affected children of all ages. Polytherapy was significantly more frequently reported for valproic acid with fatal outcome (58%) compared with non-fatal outcome (34%).
Conclusion
Hepatotoxicity remains a considerable problem. The risk appears to be greatest in young children (6 years and below) but can occur at any age. Polytherapy is commonly reported and seems to be a risk factor for hepatotoxicity, pancreatitis and other serious adverse drug reactions with valproic acid. |
| first_indexed | 2025-11-14T19:31:40Z |
| format | Article |
| id | nottingham-37196 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:31:40Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-371962020-05-04T16:56:08Z https://eprints.nottingham.ac.uk/37196/ Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase Star, Kristina Edwards, I. Ralph Choonara, Imti Introduction Valproic acid is an effective first line drug for the treatment of epilepsy. Hepatotoxicity is a rare and potentially fatal adverse reaction for this medicine. Objective Firstly to characterise valproic acid reports on children with fatal outcome and secondly to determine reporting over time of hepatotoxicity with fatal outcome. Methods Individual case safety reports (ICSRs) for children ≤17 years with valproic acid and fatal outcome were retrieved from the WHO Global ICSR database, VigiBase, in June 2013. Reports were classified into hepatotoxic reactions or other reactions. Shrinkage observed-to-expected ratios were used to explore the relative reporting trend over time and for patient age. The frequency of polytherapy, i.e. reports with more than one antiepileptic medicine, was investigated. Results There have been 268 ICSRs with valproic acid and fatal outcome in children, reported from 25 countries since 1977. A total of 156 fatalities were reported with hepatotoxicity, which has been continuously and disproportionally reported over time. There were 31 fatalities with pancreatitis. Other frequently reported events were coma/encephalopathy, seizures, respiratory disorders and coagulopathy. Hepatotoxicity was disproportionally and most commonly reported in children aged 6 years and under (104/156 reports) but affected children of all ages. Polytherapy was significantly more frequently reported for valproic acid with fatal outcome (58%) compared with non-fatal outcome (34%). Conclusion Hepatotoxicity remains a considerable problem. The risk appears to be greatest in young children (6 years and below) but can occur at any age. Polytherapy is commonly reported and seems to be a risk factor for hepatotoxicity, pancreatitis and other serious adverse drug reactions with valproic acid. Public Library of Science 2014-10-10 Article PeerReviewed Star, Kristina, Edwards, I. Ralph and Choonara, Imti (2014) Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase. PLoS ONE, 9 (10). e108970/1-e108970/8. ISSN 1932-6203 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0108970 doi:10.1371/journal.pone.0108970 doi:10.1371/journal.pone.0108970 |
| spellingShingle | Star, Kristina Edwards, I. Ralph Choonara, Imti Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase |
| title | Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase |
| title_full | Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase |
| title_fullStr | Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase |
| title_full_unstemmed | Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase |
| title_short | Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase |
| title_sort | valproic acid and fatalities in children: a review of individual case safety reports in vigibase |
| url | https://eprints.nottingham.ac.uk/37196/ https://eprints.nottingham.ac.uk/37196/ https://eprints.nottingham.ac.uk/37196/ |